Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart
Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart
复制标题
新型姜黄素衍生物 B06 减弱高葡萄糖诱导的炎症反应有助于保护大鼠肾脏和心脏免受糖尿病致病性变化
DOI：
10.1016/j.jnutbio.2012.03.012
复制
发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Liang, Guang
中科院分区：
文献类型：
--
作者：
Pan, Yong;Zhu, Guanghui;Liang, Guang
越来越多的证据表明，炎症过程参与糖尿病并发症的发展和进展。然而，对于患有糖尿病并发症的患者的有效抗炎治疗尚未被实际确定。姜黄素是姜黄的主要成分，具有多种药理活性。以前，我们合成了一种新的姜黄素类似物（B 06），与姜黄素相比，它具有改善的药代动力学和增强的抗炎活性。本研究旨在验证B 06可以减少高糖诱导的炎症和炎症介导的糖尿病并发症的假设。在体外，预处理与B 06在5 μ M的浓度显着减少高糖诱导的炎症细胞因子在巨噬细胞中的过度表达。B 06的这种抗炎活性与其抑制c-Jun N-末端激酶/核因子κ B活化有关。在体内，尽管B 06以0.2 mg.kg（-1）.d（-1）给药6周不影响糖尿病大鼠的血糖谱，但B 06治疗的动物显示血清、肾脏和心脏中的炎性介质和肾脏巨噬细胞浸润显著降低。这伴随着糖尿病引起的肾脏和心脏结构和功能异常的减弱。综上所述，这些数据表明，新型衍生物B 06可能是通过抗炎机制治疗糖尿病并发症的潜在治疗剂，并支持通过抗炎策略在糖尿病并发症治疗中的潜在应用。(C)2013 Elsevier Inc. All rights reserved.
There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 mu M significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor kappa B activation. In vivo, despite that B06 administration at 0.2 mg.kg(-1).d(-1) for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy. (C) 2013 Elsevier Inc. All rights reserved.